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- Canoy, Dexter, et al.
(författare)
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Antihypertensive drug effects on long-term blood pressure : an individual-level data meta-analysis of randomised clinical trials
- 2022
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 108:16, s. 1281-1289
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken >= 12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use.Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.
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- Copland, Emma, et al.
(författare)
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Antihypertensive treatment and risk of cancer : an individual participant data meta-analysis
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:4, s. 558-570
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Tidskriftsartikel (refereegranskat)abstract
- Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4?2 years (IQR 3?0?5?0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0?99 [95% CI 0?95?1?04] for ACEIs; 0?96 [0?92?1?01] for ARBs; 0?98 [0?89?1?07] for 13 blockers; 1?01 [0?95?1?07] for thiazides), with the exception of calcium channel blockers (1?06 [1?01?1?11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1?00 [95% CI 0?93?1?09] for ACEIs; 0?99 [0?92?1?06] for ARBs; 0?99 [0?89?1?11] for 13 blockers; 1?04 [0?96?1?13] for calcium channel blockers; 1?00 [0?90?1?10] for thiazides). Summary Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 13 blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4 & middot;2 years (IQR 3 & middot;0 & ndash;5 & middot;0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0 & middot;99 [95% CI 0 & middot;95 & ndash;1 & middot;04] for ACEIs; 0 & middot;96 [0 & middot;92 & ndash;1 & middot;01] for ARBs; 0 & middot;98 [0 & middot;89 & ndash;1 & middot;07] for 13 blockers; 1 & middot;01 [0 & middot;95 & ndash;1 & middot;07] for thiazides), with the exception of calcium channel blockers (1 & middot;06 [1 & middot;01 & ndash;1 & middot;11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1 & middot;00 [95% CI 0 & middot;93 & ndash;1 & middot;09] for ACEIs; 0 & middot;99 [0 & middot;92 & ndash;1 & middot;06] for ARBs; 0 & middot;99 [0 & middot;89 & ndash;1 & middot;11] for 13 blockers; 1 & middot;04 [0 & middot;96 & ndash;1 & middot;13] for calcium channel blockers; 1 & middot;00 [0 & middot;90 & ndash;1 & middot;10] for thiazides). Interpretation We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.
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| 4. |
- Gamborg, Michael, et al.
(författare)
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Birth weight and systolic blood pressure in adolescence and adulthood : meta-regression analysis of sex- and age-specific results from 20 Nordic studies
- 2007
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 166:6, s. 634-645
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated the shape, sex- and age-dependency, and possible confounding of the association between birth weight and systolic blood pressure (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of which included 166,249 Swedish male conscripts. Random-effects meta-regression analyses were performed on estimates obtained from age- and sex-stratified analyses within each of the cohorts. There was an inverse association between birth weight and SBP, irrespective of adjustment for concurrent body mass index. The association was linear for males, but for females with a birth weight greater than 4 kg, SBP increased with birth weight (p < 0.01). The association was stronger in the older age groups (p < 0.05), although this could have been a birth cohort effect. The association was stronger among females than among males (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85, -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical results. This meta-analysis supports the evidence of an inverse birth weight-SBP association, regardless of adjustment for concurrent body size. It also reveals important heterogeneity in the shape and strength of the association by sex and age.
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| 5. |
- Nazarzadeh, Milad, et al.
(författare)
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Blood pressure lowering and risk of new-onset type 2 diabetes : an individual participant data meta-analysis
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10313, s. 1803-1810
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.MethodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of followup in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.Findings145 939 participants (88 500 [60.6%] men and 57 429 [39.4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4.5 years (IQR 2.0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0.89 [95% CI 0.84-0.95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0.84 [95% 0.76-0.93]) and angiotensin II receptor blockers (RR 0.84 [0.76-0.92]) reduced the risk of new-onset type 2 diabetes; however, the use of beta blockers (RR 1.48 [1.27-1.72]) and thiazide diuretics (RR 1.20 [1.07-1.35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1.02 [0.92-1.13]).InterpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.
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| 6. |
- Patel, Swatee P., et al.
(författare)
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Associations between pre-pregnancy obesity and asthma symptoms in adolescents
- 2012
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 66:9, s. 809-814
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Tidskriftsartikel (refereegranskat)abstract
- Background The high prevalence of children's asthma symptoms, worldwide, is unexplained. We examined the relation between maternal pre-pregnancy weight and body mass index (BMI), and asthma symptoms in adolescents.Methods Data from 6945 adolescents born within the Northern Finland Birth Cohort 1986 were used. Prospective antenatal and birth outcome data, including maternal pre-pregnancy weight and BMI, and asthma symptoms in adolescent offspring at age 15-16 years, were employed. Logistic regression analyses were performed to examine the associations between relevant prenatal factors and asthma symptoms during adolescence.Results Current wheeze (within the past year) was reported by 10.6% of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre-pregnancy BMI was a significant predictor of wheeze in the adolescents (increase per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze; 3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9 to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile, also significantly increased the odds of current wheeze in the adolescent by 20% (95% CI 4 to 39), and adjusting for potential confounders further increased the risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma. Furthermore, these significant associations were observed only among adolescents without parental history of atopy but not among those with parental history of atopy.Conclusions The association demonstrated here between maternal pre-pregnancy overweight and obesity, and asthma symptoms in adolescents suggests that increase in asthma may be partly related to the rapid rise in obesity in recent years.
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| 7. |
- Pinho-Gomes, Ana-Catarina, et al.
(författare)
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Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation : An individual participant data meta-analysis
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. Methods and findings The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. Conclusions In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF. Author summary Why was this study done? Atrial fibrillation (AF) is the most common cardiac arrhythmia across the world and is strongly associated with future vascular disease, particularly stroke. Blood pressure (BP) lowering is an established strategy for prevention of vascular disease, but whether patients with AF benefit similarly from pharmacological BP reduction is not well understood. What did the researchers do and find? We compared the preventive effect of BP-lowering treatment on cardiovascular outcomes in patients with and without AF at baseline. We conducted an individual participant data meta-analysis using published and unpublished data from large randomised clinical trials (22 trials involving 188,570 patients). We showed that BP-lowering treatment reduced the risk of a major cardiovascular events with no evidence that effects differed according to the presence or absence of AF at baseline. The relative risk reductions were proportional to the intensity of BP reduction in individuals with and without AF. In individuals with AF, the relative risk reduction was comparable irrespective of whether baseline systolic BP was under or over the conventional treatment threshold of 140 mm Hg. What do these findings mean? BP-lowering treatment reduces the risk of major cardiovascular events in patients with AF to a similar extent to that of patients without AF. Pharmacological BP-lowering treatment for prevention of cardiovascular events should be recommended as part of care for patients with AF.
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